The overall goal of this research project is to investigate some neuropharmacological mechanisms of narcotic action and neurophysiological concomitants of withdrawal in the central nervous system (CNS). I will measure responses of spinal sensory neurons to various stimuli, and evaluate changes in these responses induced by acute and chronic drug treatment and by termination of chronic drug treatment. Results will quantify drug effects, tolerance to the effects and dependence on the drug. More specifically, I propose to study the sensory inhibitory action of the substantia gelatinosa (SG) of the spinal cord dorsal horn using newly developed electrophysiological and statistical techniques. This CNS structure has been proposed as part of an endogenous system for pain control. I will perform the following experiments: (1) Record SG responses to noxious and non-noxious electrical, mechanical and thermal stimuli delivered peripehrally; (2) Observe alteration of these responses by a) acute administration of narcotics and muscarinic agents administered to the spinal cord, systemically, and by microinjection in the midbrain; b) acute and chronic systemic administration of morphine and phencyclidine; c) withdrawal from the agents in b); (3) Measure behaviorally the analgesic or hyperalgesic effects of the above treatments. The results of this investigation may ultimately be important to the future management of chronic and acute pain in humans and of the distress accompanying withdrawal from drugs of abuse.